Experiencing disasters causes severe mental disorders, among which post-traumatic stress disorder (PTSD) is the most common. We conducted a longitudinal study to examine the effect of 5-hydroxyl tryptamine transporter gene-linked polymorphic region (5-HTTLPR) genotype on child and adolescent PTSD symptom course after the 2008 Wenchuan Earthquake. We genotyped 963 participants who personally experienced the earthquake. PTSD symptoms were measured by University of California, Los Angeles PTSD reaction index at 2.5, 3.5, 4.5 and 5.5 years after the earthquake, respectively. Latent growth model was utilised to examine the main effect and gene–environment interaction effect of 5-HTTLPR on PTSD's symptom course. 5-HTTLPR genotype predicted initial PTSD symptom severity (β = 0.108, p =.019) and rates of symptom recovery (β = −0.120, p =.031) between 2.5 and 5.5 years. Compared with L′ allele carriers, those with S′S′ genotype showed higher initial symptom severity but also faster recovery rate. 5-HTTLPR genotype only predicted symptom severity at 2.5 years after the earthquake, after controlling for sex, age, ethnicity and trauma severity (β = 0.108, p =.019). This is the first evidence of the effect of 5-HTTLPR genotype on child and adolescent PTSD symptoms longitudinally, offering a novel perspective on the effect of 5-HTTLPR on PTSD symptom development following trauma exposure.